From cellular therapies to tissue reprogramming and regenerative strategies in the treatment of diabetes.

Diabetes mellitus represents a global epidemic affecting over 350 million patients worldwide and projected by the WHO to surpass the 500 million patient mark within the next two decades. Besides Type 1 and Type 2 diabetes mellitus, the study of the endocrine compartment of the pancreas is of great translational interest, as strategies aimed at restoring its mass could become therapies for glycemic dysregulation, drug-related diabetes following diabetogenic therapies, or hyperglycemic disturbances following the treatment of cancer and nesidioblastosis. Such strategies generally fall under one of the 'three Rs': replacement (islet transplantation and stem cell differentiation); reprogramming (e.g., from the exocrine compartment of the pancreas); and regeneration (replication and induction of endogenous stem cells). As the latter has been extensively reviewed in recent months by us and others, this article focuses on emerging reprogramming and replacement approaches.